The cerebral cortex, the primary site for our perception, memory, and language, is spontaneously active. While this intrinsic activity is often considered noise, recent work suggests that it holds a key secret for understanding cortical function. Remarkably, in thalamocortical slices the spatiotemporal patterns of spontaneous cortical activity are similar to the patterns triggered by thalamic input. This result suggests tha intrinsic cortical connectivity primarily drives the pattern of the cortical response. External inpt may then release this intrinsic activity pattern. However, it is crucial to validate this model in ivo where entire brain circuits are intact. The proposed Aim 1 will determine the spatiotemporal patterns of spontaneous cortical activity in the intact brain. Determining the pattern of spontaneous activity in vivo will be a starting point for future studies dissecting the microcircuiry that generates and modulates this activity. Aim 2 will address how the spontaneous activity pattern is related to the cortical response to sensory input. To achieve these aims, we will utilize a head-fixed mouse on an air-floating spherical treadmill to image neural activity in awake behaving mice. We will use fast two-photon calcium imaging to measure the activity of large populations of neurons in vivo with unprecedented precision. To deliver external inputs, visual stimulation will be generated in Matlab using the Psychophysics Toolbox. This work will help to distinguish between two views of the cortex: either primarily driven by external inputs or primarily driven by internal circuitry. This will be an advance in basic neuroscience and also relevant to human disease. As the site of so many of the brain functions that humans hold dear, the cortex is also the target of many devastating neurologic and psychiatric diseases. By increasing our understanding of cortical function, this project will help lay the foundation for understanding the cortical dysfunction that underlies so much human suffering.